Longtime Science reporter Jon Cohen has earned a reputation as one of the most perceptive observers of HIV/AIDS research. In his recent book, Shots in the Dark: The Wayward Search for an AIDS Vaccine, (Norton and Co., 2001) he analyzed the disorganization and lack of coordination in the AIDS vaccine research effort. He argued for creation of a "March of Dollars," an entity that would play a role similar to that of the March of Dimes in developing a polio vaccine: keeping an eye on the whole field and making sure that gaps are filled.

AIDS Treatment News spoke with Cohen on June 20, after he spoke at a University of California San Francisco-sponsored event marking the 20th year of the AIDS epidemic.

AIDS Treatment News: In light of your suggestion for a March of Dollars, how do you look at developments since you wrote the book?

Cohen: There have been some big changes. Merck has revealed the details of their AIDS vaccine program, and it's a substantial program. I think it is the first time a big pharmaceutical has really revealed a serious, large program to find an AIDS vaccine, and that's all for the good. But it would be great to see some competition, still, and I don't see any really hot competition similar to the competition to develop antiretrovirals.

IAVI (the International AIDS Vaccine Initiative) has more money than ever, with Bill and Melinda Gates pledging an extra $100 million a year ago. And I think the world's attention toward the problem in Africa is a major shift that I hinted at the end of my book, but that has continued. I think as people concentrate on the real magnitude and scope of the epidemic and do see that more people have now died than died from the Black Plague, it increases the sense of urgency to find a vaccine.

Scientifically there haven't been any really dramatic insights into how to make a vaccine, but there have been several publications in the past year that show more and more solid protection in monkeys. That's good.

ATN: Obviously nobody has stepped forward to create a March of Dollars, but do you see any progress toward fulfilling the functions you envisioned for such an organization?

Cohen: I hear hallway whispers. My idea for a March of Dollars really was meant to be provocative. It's not that I believe there has to be a March of Dollars. I believe more is needed, and outlined a fantasy organization that I would like to see.

I see no organization attempting to fill gaps, to analyze what could be enriched, if you will, in the basic research arena. That could help. I still think it would be good for a smart group of people to meet four times a year and to freely distribute money to laboratories that they think could stimulate progress. That's not happening anywhere.

As far as a master monkey study [Cohen described at length in his book how studies of candidate vaccines using monkeys and SIV are not standardized, making it virtually impossible to compare results from tests of different products done in different labs], I don't see real momentum for it. I have heard hallway whispers of some people trying to organize such things, but have not seen it happening -- certainly not with the agenda I laid out, which is: After [candidate vaccines] work in monkeys better than others, move them into humans with the intent of taking them to efficacy trials, unless safety problems emerge.

And THAT would be a shift in the way that everything moves forward now. Everything moves forward based on immune responses in humans. Fine, let people do things that way. In addition, let's cover the other base; let's also move forward more empirically. It worked in monkeys, that's the rationale. It's not the levels of cytotoxic T-lymphocytes in human volunteers, nor levels of neutralizing antibodies; it's not all these fancy immunologic measurements. It's simply, this vaccine worked in monkeys.

ATN: You talked about the need for activism. What issues should activists be looking out for right now?

Cohen: I think it's very analogous to the drug activism arena. Activists existed when there were no drugs on the market. And what did they do? Well, they hounded the companies: "Where are you now? What's your progress now? What'd you do last week? What'd you do last month? What'd you do last year?" They wrote report cards on researchers. They kept track of where the money was moving between different people. They scrutinized the field and they followed the money. And they issued reports and were relentless. They shut down Wall Street, they shut down the NIH (U.S. National Institutes of Health). They did dramatic moves in San Francisco on the streets during the [6th] International [AIDS] Conference.

All that brought attention to the drug search and put the companies on notice that every move they make would be scrutinized, and they would be yelled at to move faster at every turn. And I think it helped.

None of that is happening. None of it. Yes, the AIDS Vaccine Advocacy Coalition is writing reports and they are good, but that is a small group of activists. And they are not employing street theater tactics. They're not receiving the type of attention that ACT UP once enjoyed, or that TAG [Treatment Action Group] enjoyed.

ATN: For people who are interested in vaccine development and where pressure might be applied, what should they be looking at?

Cohen: There are AIDS conferences that happen all the time. There are probably three or four big AIDS vaccine conferences a year. At one of them I was the only journalist -- that was at Keystone. At one of them I don't think there were any journalists there because I didn't go, the AIDS vaccine conference in Puerto Rico that was sponsored by IAVI. It was an important conference, and I don't think there was a single journalist there. I mean, hello? If this were drugs there would have been a hundred or a thousand journalists there.

And there's a big AIDS vaccine conference coming up in September in Philadelphia, and then there's another one in France. All of these conferences have a tremendous amount of information, and they should be monitored. There should be activists there. And there often are; Bill Snow [of AVAC] goes, but there are one or two activists. It is nowhere near the level warranted. [For lists of upcoming AIDS conferences, see links at: http://www.aidsnews.org/#conferences.]

So that's one place to start. Another is to read the literature, follow the journals, follow the papers that come out, and follow the companies that have programs and check in with them regularly the same way activists have done with drugs: Write reports, create documents for journalists to build on. I don't mean to be self-serving, but read my book. I say that because it's the only book out there on this topic.

ATN: What other sources of information would you recommend?

Cohen: You can look on the Web, too, at the NIH's Web site, and at IAVI's Web site. The IAVI newsletter is tremendous. It's an excellent source to keep up with what's going on.

ATN: There has been a shift away from looking for "sterilizing immunity" (complete prevention of infection) and toward looking at preventing disease. What does that mean for vaccine efficacy trials -- how big they'll need to be, how long they'll need to run?

Cohen: There are two schools of thought. I think it has profound implications. One school of thought is that it's not a big deal for efficacy trials, that enough people will become infected and will not opt to take [antiretroviral] drugs that you'll be able to get a clean answer.

Certainly, though, there's a numbers game going on. The problem is this: If people start taking drugs shortly after becoming infected, you're going to have a very hard time seeing a vaccine's impact on delaying or preventing disease because the drugs are going to confuse that. But if many people opt not to take drugs, statistically speaking you might have enough people to make an evaluation of whether the vaccine works.

Logically I would think the trials would have to become larger or they would have to go on for longer periods of time, one or the other. Any way about it, it becomes more expensive and more difficult.

And then you also have ethical issues that arise because of this that are really thorny. In poor countries that have no access to drugs right now you can get a cleaner answer. Is it ethical to stage a trial there -- even if people volunteer -- without offering the people who become infected treatment? Some people say you have to offer them treatment, it's the only ethical thing to do. Others counter, "Well, there's the principle of undue influence." Would it be unduly influencing someone's decision to join a trial if they knew that they would get treatment?

I think those are real issues. I don't have any pat answers for them. I think it's certainly a more complex picture today than it was before the advent of drugs.

ATN: Is there anything else that we should particularly watch out for in the next few months or years?

Cohen: I think one thing that's interesting now is how the line is blurring in the very definition of a vaccine. The simple way to describe a vaccine is "something that you take and then you never have the bug in you." Well that's clearly not the way that AIDS vaccine researchers are thinking about things now. A vaccine might do one of three things: It might prevent infection, it might prevent or delay disease and allow you to be infected, or it might be used after you become infected to bolster your immune system.

In the third category, that's an idea that's been around for years -- since the very first AIDS vaccine in 1986 was tested as a therapeutic, the Zagury trial. And it's still unclear that it's ever benefited anyone. But as these acutely infected studies begin to show auto-vaccination in essence -- people who go on and off drugs have their virus return [and] their immune system seems to actually benefit from a short exposure to the virus again, because when they go off drugs the next time they're more likely to contain the infection for a longer period of time. It argues very strongly for a therapeutic vaccine used in an acute infection setting with strategic treatment interruption. That's yet another version of what an AIDS vaccine might do.

It's also possible that AIDS vaccines used in conjunction with drugs will reduce the emergence of resistance. That could be another parameter that you could look at. So I think there's some much more fluid definitions of what a vaccine is or might be today than there ever has been -- by mainstream thinkers, not fringe thinkers. It's no longer on the fringe to think about therapeutic vaccination. It's now mainstream. It was very "fringie" for years.

ISSN # 1052-4207

Copyright 2001 by John S. James. Permission granted for noncommercial reproduction, provided that our address and phone number are included if more than short quotations are used.

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